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Infect. Immun. doi:10.1128/IAI.01073-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CXCL10/IP-10-mediated protection against Leishmania amazonensis infection in mice

Departments of Microbiology and Immunology, and Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch Galveston, TX 77555-1070, USA

^* To whom correspondence should be addressed. Email: lysoong{at}utmb.edu.

	Abstract

Leishmania amazonensis (La) can cause progressive disease in most inbred strains of mice. We have previously shown that La-infected C57BL/6 mice have profound impairments in expression of pro-inflammatory cytokines and chemokines and in activation of antigen-specific CD4⁺ T cells. These impairments are independent of IL-4, but partially due to IL-10 production. The precise mechanism of pathogenesis associated with La infection remains largely unresolved. Since chemokines are essential mediators of leukocyte recruitment and effector cell function, we hypothesized that these molecules are important for the initiation of early responses locally and the eventual control of the infection. In this study, we examined the role of CXCL10/IP-10 and CCL2/MCP-1 in the activation of the macrophage effector function in vitro and their efficacy in ameliorating infection in vivo. Bone marrow-derived macrophages of both BALB/c and C57BL/6 mice were treated with increasing concentrations of recombinant chemokines prior to infection with either stationary-phase promastigotes or tissue-derived amastigotes. We found that treatment with IP-10 or MCP-1 significantly reduced parasite burdens in a dose-dependent manner and triggered nitric oxide production. When susceptible C57BL/6 mice were locally injected with IP-10 following La infection, there was a significant delay in lesion development and reduction in parasite burdens, accompanied by a 7- and 3.5-fold increase in IFN- and IL-12 secretion, respectively, in re-stimulated lymph node cells. This study confirms that IP-10 plays a protective role in promoting the reduction of intracellular parasites and thereby opens new avenues for therapeutic control of non-healing cutaneous leishmaniasis in the New World.

This article has been cited by other articles:

• Vasquez, R. E., Xin, L., Soong, L. (2008). Effects of CXCL10 on Dendritic Cell and CD4+ T-Cell Functions during Leishmania amazonensis Infection. Infect. Immun. 76: 161-169 [Abstract] [Full Text]  
• Wanasen, N., MacLeod, C. L., Ellies, L. G., Soong, L. (2007). L-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival of Leishmania amazonensis Amastigotes in Macrophages. Infect. Immun. 75: 2802-2810 [Abstract] [Full Text]